Link Between the Peripheral Mononuclear Cells' Capacity to Induce Insulin Resistance and Hyperinsulinemia (IRACTIV)

Seeking a Link Between the Capacity of Peripheral Mononuclear Cells to Induce Insulin Resistance and the Development of Hyperinsulinemia in a General Population

This is a two-center proof-of-concept study, ancillary to the MetACTIV study, whose objective is to define immune activation profiles from the data of individuals followed by the Caisse Primaire d'Assurance Maladie du Gard (health insurance fund).

The IRACTIV study will include a subset of volunteers from the MetACTIV study for whom a blood sample will be taken as part of the IRACTIV study.

Study Overview

• Status: Completed
• Conditions: Insulin Resistance; Hyperinsulinism; Immune System
• Intervention / Treatment: Diagnostic test: Blood test

Detailed Description

The local health insurance fund regularly offers people who have already had a free health check-up the opportunity to re-do a check-up. This invitation will be made as part of the routine, by mail. People who have participated in the MetACTIV study will be asked to participate in the present IRACTIV study ( they will be sent an information note). That way, up to 30 volunteers who previously participated in the MetACTIV study, including 10 for whom a particular profile has been identified will be recruited again in sequence.

On the day of consultation at the Gard health insurance fund, consent will be collected from subjects who have agreed to participate. The participation of the volunteers will be reduced to this single visit and 16 mL of blood will be collected on EDTA for the purpose of this study. As in the previous MetACTIV study, this blood will be transported to the Biological Resource Center at Nîmes University Hospital. From this blood, the plasma will be frozen and stored at -80°C for subsequent determination of insulin levels under the same conditions as for the MetACTIV study. Peripheral blood mononuclear cells will be frozen and, later, cultured at the Institute of Human Genetics in complete medium for 48 hours. The effect of the supernatants of these cultures on Akt phosphorylation in HepG2 cells exposed to 10nM of insulin will then be quantified by two different techniques (Western Blot and ELISA). This effect will be expressed as a percentage of inhibition compared to the phosphorylation of Akt induced by insulin alone. The insulin slope between the measurement performed in the MetACTIV study and this IRACTIV study will also be calculated and compared to the peripheral blood mononuclear cells ability to induce insulin resistance in vitro.

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Anissa MEGZARI; Phone Number: +33 4.66.68.42.36; Email: drc@chu-nimes.fr
• Study Contact Backup: Name: Sophie DE BOUARD, PhD; Phone Number: +33 4.66.68.42.37; Email: sophie.debouard@chu-nimes.fr

Study Locations

• France
  • Gard
    • Nîmes, Gard, France, 30000
      • Centre Hospitalier Universitaire
    • Nîmes, Gard, France, 3000
      • Caisse Primaire d'Assurance Maladie du Gard

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Individuals who participated in the MetACTIV study.
• Profile 2 subgroup-specific inclusion criteria:
• MetACTIV study individual with a Profile 2.
• Persons who have given free informed consent.
• Persons who have signed the consent form.
• Persons affiliated to or benefiting from a health insurance plan.
• Adults (≥18 years of age).

Exclusion Criteria:

• Persons participating in Category 1 research involving human subjects
• Persons in an exclusion period as determined by another study.
• Persons under court protection, guardianship or trusteeship.
• Persons who are incapable of giving consent.
• Persons for whom it is impossible to give clear information.
• Pregnant, parturient or breastfeeding woman.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Health Services Research
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 10 patients with high insulin levels (13.3 ± 9.2 microU/mL) and markers of metabolic syndrome; These are individuals who were isolated from the previous MetACTIV study due to their specific immune profile (Profile 2) defined by 43 immune activation markers and characterized by a high percentage of differentiated T cells and activated T cells.	Diagnostic test: Blood test; Sixteen mL of blood will be collected on EDTA for the purpose of this study
Active Comparator: 20 patients with other immune profiles	Diagnostic test: Blood test; Sixteen mL of blood will be collected on EDTA for the purpose of this study

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Fasting blood glucose	Fasting blood glucose will be measured during a routine health evaluation and measured in mM/L.	Day 0
End-of-study insulinemia	The amount of insulin in the blood of patients will be measured during a routine health evaluation and measured in µU/L.	Month 18
Effect of peripheral blood mononuclear cell supernatant on intensity of the signal induced by insulin in hepatocytes.	Peripheral blood mononuclear cells are isolated on a Ficoll gradient and frozen. These frozen peripheral blood mononuclear cells will be sent to the Institute of Human Genetics for culture and supernatants will be recovered after 48 hours. The effect of these supernatants on insulin signaling will then be tested. To do so, they will be added or not to cultured HepG2 cells stimulated 24 hours later by 10nM insulin. After stimulation, HepG2 cells will be lysed and their total Akt and phosphorylated Akt content measured by ELISA and Western Blot. The proportion of phosphorylated Akt in HepG2 cells exposed to peripheral blood mononuclear cells supernatant will be compared with the proportion of phosphorylated Akt in HepG2 cells not exposed to peripheral blood mononuclear cells supernatant and expressed as the percentage of insulin signaling inhibition induced by the peripheral blood mononuclear cells supernatant.	Hour 48

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
A. Percentage inhibition of Akt phosphorylation in Profile 2 patients compared with other immune profiles.	The decrease in signal intensity induced in hepatocytes by insulin induced by peripheral blood mononuclear cell supernatant from volunteers with Profile 2 will be compared to the decrease in this intensity induced by peripheral blood mononuclear cell supernatant from volunteers with another immune activation Profile. Measured as a percentage.	Hour 48
B. Increase in insulinemia over time in Profile 2 patients compared with other immune profiles.	Insulinemia in Profile 2 volunteers, measured in µU/mL, will be compared with that of other immune profiles.	Month 18

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Age of Profile 2 patients	In years	Day 0
Weight of profile 2 patients	In kg	Day 0
Gender of Profile 2 patients	male / female	Day 0
Waist measurement of Profile 2 patients	In cm	Day 0
Hip circumference of Profile 2 patients	In cm	Day 0
Systolic blood pressure in Profile 2 patients	In mmHg	Day 0
Diastolic blood pressure in Profile 2 patients	In mmHg	Day 0
High-density lipoproteins in Profile 2 patients	mM/L	Day 0
Low-density lipoproteins in Profile 2 patients	mM/L	Day 0
Triglycerides in Profile 2 patients	mM/L	Day 0
Hemoglobin A1c in Profile 2 patients	mM/L	Day 0

Collaborators and Investigators

• Sponsor: Centre Hospitalier Universitaire de Nīmes
• Collaborators: Caisse Primaire d'Assurance Maladie du Gard

Study record dates

Study Major Dates

• Study Start (Actual): June 27, 2022
• Primary Completion (Actual): October 5, 2022
• Study Completion (Actual): October 5, 2023

Study Registration Dates

• First Submitted: April 6, 2022
• First Submitted That Met QC Criteria: April 13, 2022
• First Posted (Actual): April 15, 2022

Study Record Updates

• Last Update Posted (Estimated): November 20, 2023
• Last Update Submitted That Met QC Criteria: November 17, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: Insulin resistance
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Insulin Resistance; Hyperinsulinism
• Other Study ID Numbers: NIMAO/2020-1/PC-01; 2021-A03189- 32 (Other Identifier: EudraCT)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No